Sex-specific differences in cytokine signaling pathways in circulating monocytes of cardiovascular disease patients.

Autor: Lu C; Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht UMC+, Maastricht University, Maastricht, the Netherlands., Donners MMPC; Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht UMC+, Maastricht University, Maastricht, the Netherlands. Electronic address: marjo.donners@maastrichtuniversity.nl., Karel J; Department of Advanced Computing Sciences, Maastricht University, Maastricht, the Netherlands., de Boer H; Department of Internal Medicine (Nephrology), Leiden UMC, Leiden, the Netherlands., van Zonneveld AJ; Department of Internal Medicine (Nephrology), Leiden UMC, Leiden, the Netherlands., den Ruijter H; Laboratory for Experimental Cardiology, Department of Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., Jukema JW; Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands; Netherlands Heart Institute, Utrecht, the Netherlands., Kraaijeveld A; Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands., Kuiper J; Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, the Netherlands., Pasterkamp G; Circulatory Health Research Center, UMC, Utrecht, the Netherlands., Cavill R; Department of Advanced Computing Sciences, Maastricht University, Maastricht, the Netherlands., Perales-Patón J; Institute for Computational Biomedicine, Faculty of Medicine, Heidelberg University and Heidelberg University Hospital, Heidelberg, Germany; Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany; Joint Research Centre for Computational Biomedicine (JRC COMBINE), Faculty of Medicine, RWTH Aachen University, Aachen, Germany., Ferrannini E; Consiglio Nazionale Delle Ricerche (CNR) Institute of Clinical Physiology, Pisa, Italy., Goossens P; Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht UMC+, Maastricht University, Maastricht, the Netherlands., Biessen EAL; Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht UMC+, Maastricht University, Maastricht, the Netherlands; Institute for Molecular Cardiovascular Research, RWTH Aachen University, Aachen, 52074, Germany.
Jazyk: angličtina
Zdroj: Atherosclerosis [Atherosclerosis] 2023 Nov; Vol. 384, pp. 117123. Date of Electronic Publication: 2023 Apr 14.
DOI: 10.1016/j.atherosclerosis.2023.04.005
Abstrakt: Background and Aims: This study aims to identify sex-specific transcriptional differences and signaling pathways in circulating monocytes contributing to cardiovascular disease.
Methods and Results: We generated sex-biased gene expression signatures by comparing male versus female monocytes of coronary artery disease (CAD) patients (n = 450) from the Center for Translational Molecular Medicine-Circulating Cells Cohort. Gene set enrichment analysis demonstrated that monocytes from female CAD patients carry stronger chemotaxis and migratory signature than those from males. We then inferred cytokine signaling activities based on CytoSig database of 51 cytokine and growth factor regulation profiles. Monocytes from females feature a higher activation level of EGF, IFN1, VEGF, GM-CSF, and CD40L pathways, whereas IL-4, INS, and HMGB1 signaling was seen to be more activated in males. These sex differences were not observed in healthy subjects, as shown for an independent monocyte cohort of healthy subjects (GSE56034, n = 485). More pronounced GM-CSF signaling in monocytes of female CAD patients was confirmed by the significant enrichment of GM-CSF-activated monocyte signature in females. As we show these effects were not due to increased plasma levels of the corresponding ligands, sex-intrinsic differences in monocyte signaling regulation are suggested. Consistently, regulatory network analysis revealed jun-B as a shared transcription factor activated in all female-specific pathways except IFN1 but suppressed in male-activated IL-4.
Conclusions: We observed overt CAD-specific sex differences in monocyte transcriptional profiles and cytokine- or growth factor-induced responses, which provide insights into underlying mechanisms of sex differences in CVD.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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